Apolipoprotein E gene polymorphism and previous alcohol withdrawal seizures

Aim of this study was to investigate the possible association of apolipoprotein E (ApoE) gene polymorphism with a history of alcohol withdrawal seizures. We included 194 patients with alcohol dependence who were divided into patients with (SZ+) and without (SZ-) previous alcohol withdrawal seizures. ApoE genotypes were determined using PCR. For statistical analysis we examined the number of ApoE alleles (ApoE2: n=36; ApoE3: n=311; ApoE4: n=41). A significant positive association with a positive history of withdrawal seizures (SZ+) was found in the ApoE3 allele group (Fisher's exact test: p=0.006) while a significant negative association was observed in the ApoE2 allele group (Fisher's exact test: p=0.029). For the ApoE4 allele group no significant differences were found regarding a history of withdrawal seizures. Our findings suggest an association between the apolipoprotein E3 gene variant and an elevated risk of alcohol withdrawal seizures. These preliminary results must be validated in further studies.     

Fibrin clot structure in patients with end-stage renal disease

Fibrin clots with reduced permeability, increased clot stiffness and reduced fibrinolysis susceptibility may predispose to cardiovascular disease (CVD). Little is known, however, about the structure of fibrin clots in patients with end-stage renal disease (ESRD). These patients suffer from a high risk of CVD in addition to their chronic low-grade inflammation. Using permeability, compaction and turbidity studies in 22 ESRD patients and 24 healthy controls, fibrin clots made from patient plasma were found to be less permeable (p < 0.001), less compactable (p < 0.001), and less susceptible to fibrinolysis (p < 0.001) than clots from controls. The maximum rate of turbidity increase was also higher for the patients than controls (p < 0.001), and scanning electron microscopy revealed higher clot density of fibrin fibers in clots from patients than clots from controls (p < 0.001). Patients had higher plasma concentrations of fibrinogen, C-reactive protein and interleukin 6 than controls. These plasma markers of inflammation correlated significantly with most of the fibrin structure characteristics observed in the patients. In contrast, plasma markers of azothemia showed no such correlations. The results suggest that in ESRD patients fibrin clots are significantly different from healthy controls, and that the fibrin structure characteristics in the patients are associated primarily with the inflammatory plasma milieu rather than with level of azothemia.     

A psychiatric and social matched case series comparison of victims of criminal homicide and homicide perpetrators in Sweden

The aim of the present study was to compare the psychosocial profiles of criminal homicide victims with those of a matched sample of perpetrators. The hypothesis was that chance determines whether someone becomes a victim or a perpetrator. In a retrospective examination of forensic psychiatric records as well as hospital records, the following variables were studied: nationality, education, substance abuse and psychiatric diagnoses. A comparative study was performed of 88 perpetrators and 83 victims in Sweden during a time period of 17 years (1978-1994). All subjects had been treated as psychiatric inpatients before the homicide. The results support the hypothesis that perpetrators and victims of homicide are similar with regard to psychiatric morbidity and social functioning. The majority were born in Sweden, and the educational level was low in both groups. Substance abuse was common in both groups: 96.7% of male and 65.3% of female victims compared with 76.6% of male and 75% of female perpetrators. Many in both of the groups had criminal records. The only major difference between the groups was recorded for psychotic disorder diagnoses, with a higher rate among perpetrators as well as a lower rate of substance abuse in this group.     

Age-specific familial risks of psychotic disorders and schizophrenia: a nation-wide epidemiological study from Sweden

OBJECTIVE: This study analyzed men and women separately by age at hospital diagnosis of psychotic disorder or schizophrenia and by maternal or paternal disease after taking several possible confounders into account. METHODS: The Multigeneration Register, in which all men and women born in Sweden from 1932 onwards are registered together with their parents, was linked to hospital data. This yielded 21,199 male and 19,029 female cases of psychotic disorders in addition to 12,799 paternal and 23,021 maternal cases of psychotic disorders (including schizophrenia). Standardized incidence ratios (SIRs) were calculated as the ratio of observed and expected number of cases among men and women with mothers and/or fathers affected by psychotic disorders or schizophrenia, compared with men and women whose mothers and/or fathers were not affected by psychotic disorders or schizophrenia. RESULTS: The overall significant SIRs among men and women with a mother, father or both parents hospitalized for psychotic disorder varied between 2.86 and 20.30. Maternal transmission of psychotic disorder was stronger than paternal, and the highest SIRs were found in the youngest age groups. Similar results were found when the subgroup schizophrenia was analyzed separately. Maternal or paternal schizophrenia implied higher risks for the offspring than maternal or paternal psychotic disorders. CONCLUSIONS: Hereditary factors have a strong influence on the onset of psychotic disorders and schizophrenia. Young people and individuals with both parents affected by these diseases need special attention as their SIRs were particularly increased.     

Sickness absence and disability pension in a cohort of employees initially on long-term sick leave due to psychiatric disorders in Sweden

Background Over the last decade sickness absence and disability pension (DP) due to psychiatric disorders have increased considerably in Western countries. The scientific knowledge base about prognoses for such absences is very limited, but employers and clinicians often predict them to be very long. The aim of this study was to investigate sickness absence and disability pension in a cohort of employees who initially were on long-term sick leave due to psychiatric disorders, with regard to gender, age, socioeconomic status, and previous sickness absence. Methods The cohort included 4,891 employees in Sweden, who, in 1999 were aged 20–61 and had a new sick-leave spell >90 days with a psychiatric disorder. Retrospective and prospective registry data on sickness absence and DP for 1996–2002 were obtained. Logistic regressions were performed to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for having a low, intermediate, or high level of sickness absence (<17, 17–90, and 91–365 days, respectively) or DP in 2002. Results The mean number of sick-leave days per person per year 3 years prior to inclusion was low; 17 days, but had increased to 211 days by 2000. In 2002, 26% had been granted DP, significantly higher rate among men, while a higher rate of the women had long-term sickness absence. Of all 4,891 subjects, 35% had <17 sick-leave days in 2002. The OR of having low, intermediate, or long-term sickness absence decreased with age. The reverse was found for obtaining DP, for which also low socioeconomic status was an independent predictor of an increased risk (OR = 3.40, CI 2.28–5.08). Conclusions Employees with long-term sick leave due to psychiatric disorders did not have a high level of sickness absence in the 3 years prior to inclusion in the study. Also, 3 years after inclusion, only 35% had very low levels of sickness absence, whereas 26% had been granted DP. Employees who were aged 55–61 showed the lowest risk of sick leave but the highest risk of DP. Low SES was a significant predictor of DP in 2002.     

Increase in [11C]vorozole binding to aromatase in the hypothalamus in rats treated with anabolic androgenic steroids

In the present study, we investigated the alteration of aromatase expression in the brain by anabolic androgenic steroid treatment in male rats. The rats were given nandrolone decanoate (15 mg/kg/day) for 14 days, and the brains were used for autoradiography with [C]vorozole, which has been developed as a positron emission tomography tracer for aromatase by our group. The results indicated a significant increase of [C]vorozole binding by anabolic androgenic steroids in the bed nucleus of the stria terminalis and preoptic area. In contrast, no significant change of [C]vorozole binding was observed in the medial amygdala. Our results suggest that aromatase is significantly upregulated in the bed nucleus of the stria terminalis and preoptic area by anabolic androgenic steroids and also suggest that androgens regulate aromatase differently in these structures compared with the medial amygdala.     

Ostreolysin induces sustained contraction of porcine coronary arteries and endothelial dysfunction in middle- and large-sized vessels

Ostreolysin (Oly), a cytolytic and cardiotoxic protein from the oyster mushroom (Pleurotus ostreatus), is lethal for mice with an LD₅₀ of 1170 μg/kg following intravenous application. Its cardiotoxicity is associated with hyperkalemia, which is probably a consequence of potassium released from the lysed cells. Moreover, sub-micromolar concentrations of Oly induce a concentration-dependent increase in rat aortic ring tension, suggesting that ischaemia, and consequent hypoxic injury of cardiomyocytes, could also derive from vasospasm induced by this toxic protein.The purpose of the present study was to demonstrate histopathological lesions caused by Oly after parenteral application to rats, and to define the mechanisms of Oly-induced vasoconstriction using inhibitors verapamil, lanthanum chloride, and selective endothelin receptor antagonist TBC3214, which have different molecular targets, in vitro on porcine coronary artery rings. We found that Oly causes endothelial injury with perivascular oedema in the heart and lungs, as well as myocardial haemorrhages in rats. Treatment of porcine coronary artery rings with Oly causes concentration-dependent vasoconstriction and prevents endothelium-mediated relaxation. Using TBC3214 as a selective blocker of the endothelin A receptor, we showed that vasoconstriction induced by Oly was independent of endothelin release and its effects. Verapamil (1 μM) greatly reduced Oly-evoked contractions of porcine coronary artery rings, while lanthanum abolished them completely. These results provide evidence that the contraction of coronary arteries by Oly is due mainly to the increased influx of Ca²⁺ from the extracellular space through voltage-dependent L-type Ca²⁺ channels and cation non-selective channels. Experiments suggest that Oly damages endothelial cells both in vitro and in vivo, and probably exhibits direct contractile effects on coronary smooth muscle cells.     

Circulating angiogenic cytokines and stem cells in patients with severe chronic ischemic heart disease — Indicators of myocardial ischemic burden?

BackgroundAngiogenic growth factors and stem cell therapies have demonstrated varying results in patients with chronic coronary artery disease. A reason could be that these mechanisms are already up-regulated due to reduced blood supply to the myocardium. The objective of this study was to examine if plasma concentrations of circulating stem cells and angiogenic cytokines in patients with severe stable chronic coronary artery disease were correlated to the clinical severity of the disease.MethodsFifty-four patients with severe coronary artery disease and reversible ischemia at stress myocardial perfusion scintigraphy were prospectively included. The severity of the disease was quantified by an exercise tolerance test, Canadian Cardiovascular Society angina classification, and Seattle Angina Pectoris Questionnaire. Fifteen persons without coronary artery disease served as control subjects.ResultsPlasma concentration of VEGF-A, FGF-2, SDF-1, and circulating CD34+ and CD34−/CD45− cells were similar in the two groups, but early stem cell markers (CD105, CD73, CD166) and endothelial markers (CD31, CD144, VEGFR2) were significantly different between patients and control subjects (p < 0.005 − 0.001). Diabetic patients had higher concentration of SDF-1 (2528 vs. 2150 pg/ml, p = 0.004). We found significant correlations between both VEGF-A, FGF-2, and CD34+ to disease severity, including degree of reversible ischemia, angina stability score, and exertional dyspnoea.ConclusionsPlasma concentrations of circulating stem cells and angiogenic cytokines have large inter-individual variations, which probably exclude them from being useful as indicators of myocardial ischemic burden.     

Human combinatorial libraries yield rare antibodies that broadly neutralize hepatitis C virus

One way to dissect the antibody response to an invading microorganism is to clone the antibody repertoire from immune donors and subsequently characterize the specific antibodies. Recently, methodological advances have allowed investigations of neutralizing antibodies against hepatitis C virus (HCV) in vitro. We have investigated three human mAbs, previously isolated from an individual infected with HCV of genotype 2b, that are known to cross-react in a binding assay to the envelope E2 protein of genotypes 1a and 1b. We now report that two of them have a neutralizing activity with a breadth not previously observed. Indeed, mAbs 1:7 and A8 recognized E2 from all of the six major genotypes, and they neutralized retroviral pseudoparticles [HCV pseudoparticles (HCVpp)] carrying genetically equally diverse HCV envelope glycoproteins. Importantly, these antibodies were also able to neutralize the cell culture infectious HCV clone JFH-1 in vitro, with IC(50) values of 60 ng/ml and 560 ng/ml, respectively. The conformational epitopes of these two broadly reactive antibodies were overlapping yet distinct and involved amino acid residues in the 523-535 region of E2, known to be important for the E2-CD81 interaction. The third antibody clone, representing a dominant population in the initial screen for these antibodies, was less broadly reactive and was unable to neutralize the genotype 2a infectious clone JFH-1. Our results confirm at the clonal level that broadly neutralizing human anti-HCV antibodies can be elicited and that the region amino acids 523-535 of the HCV envelope glycoprotein E2 carries neutralizing epitopes conserved across all genotypes.